Abstract
The importance of natural killer (NK) cells in innate immune responses against tumors or viral infections enhances the appeal of NK cell-based immunotherapeutic approaches. We have recently reported that baculovirus (BV)-infected dendritic cells (DCs; BV-DCs) induce antitumor immunity against established tumors in mice. These antitumor effects were CD8+ T-cell and NK cell dependent; however, they were found to be CD4+ T-cell independent. In this study, we investigated the involvement of Toll-like receptor 9 (TLR9) in the process of BV recognition by NK cells. We found that BV directly stimulated NK cells, induced the expression of the activation marker CD69 and promoted interferon-gamma (IFN-γ) production and cytotoxicity. Moreover, TLR9 knockout in mice (tlr9−/− NK cells) inhibited NK cell responses to BV, indicating that TLR9 may have a relevant role in the BV-induced upregulation of NK cell functions. Our data demonstrated for the first time that NK cells directly recognize BV via TLR9, which provides opportunities for the use of this technique as an effective tool for BV-based immunotherapies against malignancies.
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Acknowledgements
We thank A. Fujihira for providing excellent technical assistance. We thank Professor N Miyano-Kurosaki for discussions and for comments on the manuscript. This work was supported, in part, by a grant from the Supporting Program for Creating University Ventures from the Japanese Science and Technology Agency, a grant from the Research and Development Program for New Bio-industry Initiatives from the Ministry of Agriculture and Forestry and the Fisheries of Japan, and a Grant-in-Aid for High Technology Research (No. 09309011) from the Ministry of Education, Science, Sports and Culture of Japan.
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Moriyama, T., Suzuki, T., Chang, M. et al. Baculovirus directly activates murine NK cells via TLR9. Cancer Gene Ther 24, 175–179 (2017). https://doi.org/10.1038/cgt.2017.2
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DOI: https://doi.org/10.1038/cgt.2017.2
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